Atopy or IgE mediated allergic disease is the leading chronic disease in children; it causes 1/4 of all school absences, results in 5,000- 7,000 deaths annually in USA, and affects over 10% of the population. This problem may be prevented or its chronic effects minimized by early recognition and treatment. For this, we propose to establish an Allergy Clinical Research Center to focus the resources of the University of California, San Francisco. We will study the development of atopy in animal models and children in order to answer 2 basic questions: Does the genetically predisposed infant have the mechanism for atopic sensitization functioning at birth? Do environmental events, such as early feeding of foreign proteins (cow's milk), infections, or parasitic infestations trigger this mechanism? Infants from families with allergic disease in both parents and siblings will be observed from birth to 5 years, with periodic evaluations of serum immunoglobulins and specific IgE antibodies, histamine release from leukocytes, cellular immunity with H3 thymidine uptake and MIF release by lymphocytes, cyclic AMP content of leukocytes and autonomic status. Effects of external environmental events will be studied by challenge with an early antigenic load (cow's milk feeding), during infections, or exposure to parasitic infestation (house dust mite). Such studies will be supplemented by observing experimental conditions in animal models. This multidisciplinary study of atopy will provide a rational approach to the prevention and treatment of allergies in children providing an understanding of the mechanisms which initiate these allergic diseases.